We utilized a sensitive, quantitative assay for iron regulatory protein 2 which allows study of endogenous iron regulatory protein 2 degradation in HEK293A cells under more physiologic conditions. We found that under these conditions the proteasome plays only a minor role in the degradation of iron regulatory protein 2, with almost all the iron regulatory protein 2 being degraded by a non-proteasomal pathway. Multiple attempts utilizing a variety of molecular biological and biochemical techniques failed to identify the protease responsible. The project was terminated in February, 2012.